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https://www.readbyqxmd.com/read/28640632/gut-microbiota-nitric-oxide-and-microglia-as-pre-requisites-for-neurodegenerative-disorders
#1
Joyce Ka Yu Tse
Regulating fluctuating endogenous nitric oxide (NO) levels is necessary for proper physiological functions. Aberrant NO pathways are implicated in a number of neurological disorders, including Alzheimer's Disease (AD) and Parkinson's Disease. The mechanism of NO in oxidative and nitrosative stress with pathological consequences involves reactions with reactive oxygen species (e.g. superoxide) to form the highly reactive peroxynitrite, hydrogen peroxide, hypochloride ions and hydroxyl radical. NO levels are typically regulated by endogenous nitric oxide synthases (NOS), and inflammatory iNOS is implicated in the pathogenesis of neurodegenerative diseases, in which elevated NO mediates axonal degeneration and activates cyclooxygenases to provoke neuroinflammation...
June 22, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28640450/network-supervision-of-adult-experience-and-learning-dependent-sensory-cortical-plasticity
#2
David T Blake
The brain is capable of remodeling throughout life. The sensory cortices provide a useful preparation for studying neuroplasticity both during development and thereafter. In adulthood, sensory cortices change in the cortical area activated by behaviorally relevant stimuli, by the strength of response within that activated area, and by the temporal profiles of those responses. Evidence supports forms of unsupervised, reinforcement, and fully supervised network learning rules. Studies on experience-dependent plasticity have mostly not controlled for learning, and they find support for unsupervised learning mechanisms...
June 18, 2017: Comprehensive Physiology
https://www.readbyqxmd.com/read/28638920/-a-study-on-toxic-effects-of-sodium-salicylate-on-rat-cochlear-spiral-ganglion-neurons-dopamine-receptors-mediate-expressions-of-nmda-and-gabaa-receptors
#3
Ting-Jia Wei, Hui-Ying Chen, Xi Huang, Jing-Jin Weng, Jiang-Yuan Qin, Ji-Ping Su
The aim of the present study was to observe whether dopamine receptor (DR) was involved in the effects of sodium salicylate (SS) on the expressions of N-methyl-D-aspartic acid (NMDA) and γ-aminobutyric acid (GABA) receptors in rat cochlear spiral ganglion neurons (SGNs). Forty-eight hours after primary culture of rat SGNs, immunofluorescence technique was applied to detect expressions of DR1 and DR2, the two subtypes of dopamine receptors. Western blot was performed to assess NMDA receptor NR1 subunit and GABAA receptor subunit α2 (GABRα2) protein expressions in the SGNs after the treatments of SS alone or in combination with DR antagonists...
June 25, 2017: Sheng Li Xue Bao: [Acta Physiologica Sinica]
https://www.readbyqxmd.com/read/28637049/protecting-oligodendrocytes-by-targeting-non-glutamate-receptors-as-a-new-therapeutic-strategy-for-ischemic-stroke
#4
Pan Luo, Dong Liu, Lianjun Guo
Ischemic stroke has many devastating effects within the brain. At the cellular level, excitotoxicity has been a popular pharmacological target for therapeutics. To date, many clinical trials have been performed with drugs that target excitatory neurotransmitter receptors, such as NMDA receptor agonists. The results, however, have been lackluster. Most efforts to understand the impacts of excitotoxicity on the brain have focused primarily on neurons, and to a lesser degree, on gliocytes as cellular targets. Recent evidence suggests that oligodendrocytes (OLGs), the myelin-forming cells in the central nervous system, are damaged by ischemia in a manner completely different from that in neurons...
June 21, 2017: Pharmacology
https://www.readbyqxmd.com/read/28635080/neuroadaptations-of-presynaptic-and-postsynaptic-gabab-receptor-function-in-the-paraventricular-nucleus-in-response-to-chronic-unpredictable-stress
#5
Yonggang Gao, Jing-Jing Zhou, Yun Zhu, Li Wang, Therese A Kosten, Xiangjian Zhang, De-Pei Li
BACKGROUND: Chronic stress induces an impaired GABAA (γ-aminobutyric acid type A) receptor-mediated inhibition in the hypothalamic paraventricular nucleus (PVN). It is not clear whether GABAB receptor function is altered in chronic stress. We hypothesize that chronic stress alters GABAB receptor function in PVN corticotrophin-releasing hormone (CRH) neurons to control hypothalamus-pituitary-adrenal (HPA) axis activity. EXPERIMENTAL APPROACH: Whole cell patch-clamp recording was performed on PVN-CRH neurons expressing eGFP driven by CRH promoter in brain slices from unstressed rats and rats that had been subjected to chronic unpredictable mild stress (CUMS)...
June 20, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28632204/successful-pharmacotherapy-for-the-treatment-of-severe-feeding-aversion-with-mechanistic-insights-from-cross-species-neuronal-remodeling
#6
W G Sharp, A G Allen, K H Stubbs, K K Criado, R Sanders, C E McCracken, R G Parsons, L Scahill, S L Gourley
Pediatric feeding disorders affect up to 5% of children, causing severe food intake problems that can result in serious medical and developmental outcomes. Behavioral intervention (BI) is effective in extinguishing feeding aversions, and also expert-dependent, time/labor-intensive and not well understood at a neurobiological level. Here we first conducted a double-blind, placebo-controlled trial comparing BI with BI plus d-cycloserine (DCS). DCS is a partial N-methyl-d-aspartate (NMDA) receptor agonist shown to augment extinction therapies in multiple anxiety disorders...
June 20, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28614711/dapk1-mediates-ltd-by-making-camkii-glun2b-binding-ltp-specific
#7
Dayton J Goodell, Vincent Zaegel, Steven J Coultrap, Johannes W Hell, K Ulrich Bayer
The death-associated protein kinase 1 (DAPK1) is a potent mediator of neuronal cell death. Here, we find that DAPK1 also functions in synaptic plasticity by regulating the Ca(2+)/calmodulin (CaM)-dependent protein kinase II (CaMKII). CaMKII and T286 autophosphorylation are required for both long-term potentiation (LTP) and depression (LTD), two opposing forms of synaptic plasticity underlying learning, memory, and cognition. T286-autophosphorylation induces CaMKII binding to the NMDA receptor (NMDAR) subunit GluN2B, which mediates CaMKII synaptic accumulation during LTP...
June 13, 2017: Cell Reports
https://www.readbyqxmd.com/read/28611595/mtorc1-is-a-local-postsynaptic-voltage-sensor-regulated-by-positive-and-negative-feedback-pathways
#8
Farr Niere, Kimberly F Raab-Graham
The mammalian/mechanistic target of rapamycin complex 1 (mTORC1) serves as a regulator of mRNA translation. Recent studies suggest that mTORC1 may also serve as a local, voltage sensor in the postsynaptic region of neurons. Considering biochemical, bioinformatics and imaging data, we hypothesize that the activity state of mTORC1 dynamically regulates local membrane potential by promoting and repressing protein synthesis of select mRNAs. Our hypothesis suggests that mTORC1 uses positive and negative feedback pathways, in a branch-specific manner, to maintain neuronal excitability within an optimal range...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28608233/alleviation-by-gabab-receptors-of-neurotoxicity-mediated-by-mitochondrial-permeability-transition-pore-in-cultured-murine-cortical-neurons-exposed-to-n-methyl-d-aspartate
#9
Toshihiko Kinjo, Yoshino Ashida, Hiroshi Higashi, Satoshi Sugimura, Miho Washida, Hiroki Niihara, Kiyokazu Ogita, Yukio Yoneda, Nobuyuki Kuramoto
Mitochondrial permeability transition pore (PTP) is supposed to at least in part participate in molecular mechanisms underlying the neurotoxicity seen after overactivation of N-methyl-D-aspartate (NMDA) receptor (NMDAR) in neurons. In this study, we have evaluated whether activation of GABAB receptor (GABABR), which is linked to membrane G protein-coupled inwardly-rectifying K(+) ion channels (GIRKs), leads to protection of the NMDA-induced neurotoxicity in a manner relevant to mitochondrial membrane depolarization in cultured embryonic mouse cortical neurons...
June 12, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28604219/potentiation-of-nmda-receptor-mediated-synaptic-transmission-at-the-parabrachial-central-amygdala-synapses-by-cgrp-in-mice
#10
Yuya Okutsu, Yukari Takahashi, Masashi Nagase, Kei Shinohara, Ryo Ikeda, Fusao Kato
The capsular part of the central amygdala (CeC) is called the "nociceptive amygdala," as it receives nociceptive information from various pathways, including monosynaptic input from the lateral part of the parabrachial nucleus (LPB), a major target of ascending neurons in the spinal and medullary dorsal horn. LPB-CeC synaptic transmission is mediated by glutamate but the fibers from the LPB also contain calcitonin gene-related peptide (CGRP) and the CeC is rich in CGRP-binding sites. CGRP might be released in response to strong nociception and activate these CGRP receptors...
January 2017: Molecular Pain
https://www.readbyqxmd.com/read/28602919/the-fine-tuning-of-retinocollicular-topography-depends-on-reelin-signaling-during-early-postnatal-development-of-the-rat-visual-system
#11
Rachel Antonioli-Santos, Bruna Lanzillotta-Mattos, Cecília Hedin-Pereira, Claudio Alberto Serfaty
During postnatal development, neural circuits are extremely dynamic and develop precise connection patterns that emerge as a result of the elimination of synaptic terminals, a process instructed by molecular cues and patterns of electrical activity. In the rodent visual system, this process begins during the first postnatal week and proceeds during the second and third postnatal weeks as spontaneous retinal activity and finally use dependent fine tuning takes place. Reelin is a large extracellular matrix glycoprotein able to affect several steps of brain development, from neuronal migration to the maturation of dendritic spines and use-dependent synaptic development...
June 7, 2017: Neuroscience
https://www.readbyqxmd.com/read/28596523/extrasynaptic-nmda-receptor-dependent-long-term-potentiation-of-hippocampal-ca1-pyramidal-neurons
#12
Qian Yang, Geng Zhu, Dandan Liu, Jue-Gang Ju, Zhen-Hua Liao, Yi-Xin Xiao, Yue Zhang, Naijian Chao, JieJie Wang, Weidong Li, Jian-Hong Luo, Sheng-Tian Li
In the adult mouse hippocampus, NMDA receptors (NMDARs) of CA1 neurons play an important role in the synaptic plasticity. The location of NMDARs can determine their roles in the induction of long-term potentiation (LTP). However, the extrasynaptic NMDARs (ES-NMDARs) dependent LTP haven't been reported. Here, through the use of a 5-Hz stimulation and MK-801 (an irreversible antagonist of NMDARs) in the CA1 neurons of adult mice hippocampal slices, synaptic NMDARs were selectively inhibited and NMDAR-mediated excitatory postsynaptic currents were not recovered...
June 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28594440/calcium-signalling-in-medial-intercalated-cell-dendrites-and-spines
#13
Cornelia Strobel, Robert K P Sullivan, Peter Stratton, Pankaj Sah
The amygdala plays a central role in fear conditioning and extinction. The medial intercalated (mITC) neurons are GABAergic cell clusters interspaced between the basolateral (BLA) and central amygdala (CeA). These neurons are thought to play a key role in fear and extinction, controlling the output of the CeA by feed-forward inhibition. BLA to mITC cell inputs are though to undergo synaptic plasticity, a mechanism underlying learning, which is mediated by NMDA-receptor dependent mechanisms that require changes in cytosolic calcium...
June 8, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28593436/long-term-plasticity-in-amygdala-circuits-implication-of-cb1-dependent-ltd-in-stress
#14
Bingjin Li, Tongtong Ge, Ranji Cui
The amygdala mediates many forms of emotional learning, during which the central nucleus of amygdala (CeA) functions as a major output of the amygdala by converging inputs from the basolateral nucleus (BLA) and other amygdalar subregions. However, the contribution of BLA-CeA synaptic transmission and plasticity of this transmission after exposure to emotional stimuli remains to be completely understood. Using paired recording, we simultaneously recorded BLA and CeA neurons, and observed that BLA-CeA transmission was glutamatergic...
June 7, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28592819/spatial-and-temporal-boundaries-of-nmda-receptor-hypofunction-leading-to-schizophrenia
#15
Kazu Nakazawa, Vivek Jeevakumar, Kazuhito Nakao
The N-methyl-D-aspartate receptor hypofunction is one of the most prevalent models of schizophrenia. For example, healthy subjects treated with uncompetitive N-methyl-D-aspartate receptor antagonists elicit positive, negative, and cognitive-like symptoms of schizophrenia. Patients with anti-N-methyl-D-aspartate receptor encephalitis, which is likely caused by autoantibody-mediated down-regulation of cell surface N-methyl-D-aspartate receptors, often experience psychiatric symptoms similar to schizophrenia initially...
February 3, 2017: NPJ Schizophrenia
https://www.readbyqxmd.com/read/28588297/targeted-patching-and-dendritic-ca-2-imaging-in-nonhuman-primate-brain-in-vivo
#16
Ran Ding, Xiang Liao, Jingcheng Li, Jianxiong Zhang, Meng Wang, Yu Guang, Han Qin, Xingyi Li, Kuan Zhang, Shanshan Liang, Jiangheng Guan, Jia Lou, Hongbo Jia, Bingbo Chen, Hui Shen, Xiaowei Chen
Nonhuman primates provide an important model not only for understanding human brain but also for translational research in neurological and psychiatric disorders. However, many high-resolution techniques for recording neural activity in vivo that were initially established for rodents have not been yet applied to the nonhuman primate brain. Here, we introduce a combination of two-photon targeted patching and dendritic Ca(2+) imaging to the neocortex of adult common marmoset, an invaluable primate model for neuroscience research...
June 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28588066/identification-of-aicp-as-a-glun2c-selective-nmda-receptor-superagonist-at-the-glun1-glycine-site
#17
Maja Jessen, Kristen Frederiksen, Feng Yi, Rasmus P Clausen, Kasper B Hansen, Hans Brauner-Osborne, Paul Kilburn, Anders Damholt
NMDA-type ionotropic glutamate receptors mediate excitatory neurotransmission in the central nervous system and are critically involved in brain function. NMDA receptors are also implicated in psychiatric and neurological disorders and have received considerable attention as therapeutic targets. In this regard, administration of D-cycloserine (DCS), which is a glycine site NMDA receptor agonist, can enhance extinction of conditioned fear responses. The intriguing behavioral effects of DCS have been linked to its unique pharmacological profile among NMDA receptor subtypes (GluN1/2A-D), in which DCS is a superagonist at GluN2C-containing receptors compared to glycine and a partial agonist at GluN2B-containing receptors...
June 6, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28580823/ethanol-and-the-developing-brain-inhibition-of-neuronal-activity-and-neuroapoptosis
#18
Nailya Lotfullina, Roustem Khazipov
Ethanol induces massive neuroapoptosis in the developing brain. One of the main hypotheses that has been put forward to explain the deleterious actions of ethanol in the immature brain involves an inhibition of neuronal activity. Here, we review recent evidence for this hypothesis obtained in the somatosensory cortex and hippocampus of neonatal rodents. In both structures, ethanol strongly inhibits brain activity. At the doses inducing massive neuroapoptosis, ethanol completely suppresses the early activity patterns of spindle-bursts and gamma oscillations in the neocortex and the early sharp-waves in the hippocampus...
June 1, 2017: Neuroscientist: a Review Journal Bringing Neurobiology, Neurology and Psychiatry
https://www.readbyqxmd.com/read/28580416/glua2-lacking-ampa-receptors-and-nitric-oxide-signaling-gate-spike-timing-dependent-potentiation-of-glutamate-synapses-in-the-dorsal-raphe-nucleus
#19
Samir Haj-Dahmane, Jean Claude Béïque, Roh-Yu Shen
The dorsal raphe nucleus (DRn) receives glutamatergic inputs from numerous brain areas that control the function of DRn serotonin (5-HT) neurons. By integrating these synaptic inputs, 5-HT neurons modulate a plethora of behaviors and physiological functions. However, it remains unknown whether the excitatory inputs onto DRn 5-HT neurons can undergo activity-dependent change of strength, as well as the mechanisms that control their plasticity. Here, we describe a novel form of spike-timing-dependent long-term potentiation (tLTP) of glutamate synapses onto rat DRn 5-HT neurons...
May 2017: ENeuro
https://www.readbyqxmd.com/read/28576649/anti-androgenic-effects-of-bisphenol-a-on-spatial-memory-and-synaptic-plasticity-of-the-hippocampus-in-mice
#20
Zhaoqing Fang, Qingjie Zhu, Ting Gu, Xiuying Shen, Yang Yang, Yufeng Liang, Zigui Zhang, Xiaohong Xu
Bisphenol-A (BPA) is a common environmental endocrine disruptor. Our recent studies found that exposure to BPA in both adolescent and adulthood sex-specifically impaired spatial memory in male mice. In this study, 11-week-old gonadectomied (GDX) male mice daily received subcutaneous injections of testosterone propionate (TP, 0.5mg/kg), TP and BPA (0.4 and 4mg/kg), or vehicle for 45days. The results of Morris water maze task showed that exposure to BPA did not affect the spatial memory of GDX mice but impaired that of sham (4mg/kg/day) and TP-treated GDX mice (0...
June 8, 2017: Hormones and Behavior
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